Perm Medical Journal

The COVID-19 pandemic has significantly influenced the course and clinical presentation of skin diseases. Literature data indicate frequent lesions of the mucous membranes, skin, and its adnexa following the novel coronavirus infection caused by SARS-CoV-2. The proportion of dermatoses associated with COVID-19 among infected patients reaches 20.4 %.

Based on the time of their development, skin lesions associated with coronavirus infection, are classified as early (acute), observed, within 2 to 4 weeks. These include cutaneous angiitis, morbilliform, papulosquamous, and papulovesicular rashes, drug eruptions, urticaria, and factitial lesions. These dermatoses result from the direct effect of SARS-CoV-2, its toxins and metabolites on the skin and mucous membranes and/or from a concomitant drug-induced toxic-allergic reaction. Late (chronic) skin lesions develop from 1 month to 1 year after novel coronavirus infection or within 4 weeks after vaccination. Late skin diseases exacerbated by SARS-CoV-2 include papulosquamous dermatoses, post-COVID alopecia, allergic dermatoses, collagen vascular diseases, acneiform dermatoses, nail plate changes, erythema, bullous dermatoses, and psychogenic dermatoses. The pathological effect of SARS-CoV-2 in the late stages post-infection or post-vaccination is due to the affinity of certain keratinocyte structures for the virus. The virus enters the cell, stimulates T-lymphocyte activation, enhances T-helper cell proliferation, and hyperproduction of proinflammatory cytokines and antibodies. This leads to interleukins synthesis and hyperstimulation of tissue inflammation, impairing skin cell differentiation.

A significant proportion of concomitant dermatoses and comorbid pathologies has been identified in patients with late skin lesions that developed within 1 year after SARS-CoV-2 or within 4 weeks after vaccination. Moderate to severe courses of post-COVID dermatoses and complicated clinical cases have been frequently reported. Most clinical observations have shown a predominance of widespread rashes, atypical localization, and atypical clinical presentations, with rare clinical variants being more common. Combinations of two and three dermatological nosologies in a single patient (multimorbidity) have been noted. Pathomorphosis (nosomorphosis) of papulosquamous and autoimmune skin diseases has been observed, manifesting as the evolution of one dermatosis into another.

Objective. To identify predictors of poor prognosis in patients with arterial hypertension (AH) without associated clinical conditions who have long-term post-COVID syndrome (LPS).

Materials and methods. This work presents a subanalysis of a prospective observational study, which included 258 patients with AH and LPS according to the inclusion and exclusion criteria. The incidence of fatal events and any hospitalizations was recorded throughout the follow-up period. At the end of the follow-up period, the patients were divided into 2 groups based on prognostic parameters: Group 1 included 65 patients who experienced adverse events, and Group 2 comprised 193 patients with no fatal events and hospitalizations during the observation period.

Results. In 33.7 % of patients with uncomplicated AH, the development of LPS was associated with a risk of all-cause mortality (4.6 %) and hospitalizations (95.4 %) after 22.5 ± 8.4 months of follow-up. Uncontrolled AH based on home measurement, failure to achieve the target nocturnal blood pressure (BP), and a morning systolic BP surge > 56 mm Hg increased the relative risk (RR) of an adverse prognosis in patients with AH, LPS, and no associated clinical conditions by 1.9-fold; a non-dipper/night-peaker circadian BP profile increased it by 3.2-fold; a mean 24-hour pulse pressure > 53 mm Hg increased it by 2-fold; and nocturnal masked AH increased it by
3.6-fold. Structural and functional left ventricular (LV) remodeling characterized by LV diastolic dysfunction, LV hypertrophy, elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and indicative of preclinical chronic heart failure (CHF) in patients with uncomplicated AH and LPS without symptoms and signs of circulatory insufficiency, increased the RR of an adverse prognosis by an average of 2–2.5 times. Only an estimated glomerular filtration rate (eGFR) <  60 ml/min/1.73 m² (calculated using cystatin C alone or its combination with creatinine), and a urinary protein-to-creatinine ratio >300 mg/g, indicated a poor prognosis in patients with uncomplicated AH and LPS, increasing the RR by 2.0, 1.2, and 1.8 times, respectively. The development or progression of chronic kidney disease (CKD) in patients with AH and LPS increased the RR of poor prognosis
by 2.2-fold.

Conclusions. LPS in patients with uncomplicated AH is associated with a high incidence of adverse prognosis. The predictive value for adverse outcomes in this patient population was demonstrated by indicators reflecting the uncontrolled course of AH, particularly at night and early in the morning, the presence of preclinical CHF and CKD.

Objective. To compare the efficacy of various clinical monitoring programs, including a remote monitoring system using automated interactive questionnaire.

Materials and methods. The study included 254 patients with COPD, divided into 3 dynamic monitoring groups: the main group of patients (n=77) used a remote monitoring system activities, including an interactive questionnaire; the comparison group (n=75) who used a remote monitoring system activities limited to the assessment of a number of objective parameters: a modified 6-minute walk test (6-MWT test, in steps), daily physical activity (number of steps per day) and peak expiratory flow rate, but the interactive questionnaire was not applied in this group; the control group (n=102), received standard follow-up according to routine clinical practice without remote monitoring in compliance with the Order No. 168n of the Russian Ministry of Health (dated March 15, 2022) “On approval of the Procedure for Dispensary Observation of Adults”.

Results. In the main group, where remote monitoring of interactive questionnaire data was combined with the assessment of objective disease criteria, a significant proportion of patient transition from group “E” to group “B” (a course with rare exacerbations) was revealed. In the comparison group, no significant disease rephenotyping was observed. Conversely, in the control group, a significant proportion of patients transitioned from groups “A” and “B” to group “E” (a course with frequent exacerbations). Over the 12 month follow-up period, treatment in the main group was aligned with clinical guidelines; in the comparison group, a less significant redistribution of treatment programs was observed; in the control group, the rate of treatment regimen compliance with clinical guidelines after one year did not exceed 40 %.

Conclusions. An approach combining the assessment of subjective (using an interactive questionnaire) and objective criteria for remote monitoring, improves the quality of clinical follow-up in COPD patients, allowing disease rephenotyping, timely detection of disease exacerbations, and achieving symptom control through the prompt adjustment of maintenance therapy, when required.

Objective. To evaluate the efficacy and safety of ulinastatin in patients with postoperative abdominal sepsis (AS) in intensive care units.

Materials and methods. This randomized study included 60 patients with AS divided into two groups: the ulinastatin group (n = 30) received standard intensive therapy combined with intravenous ulinastatin (200,000 IU three times daily for 3 days, followed by 100,000 IU three times daily for 4 days); the control group (n = 30) received standard intensive therapy alone. Clinical outcomes, organ dysfunction (SOFA score, Glasgow Coma Scale), laboratory markers of inflammation (CRP, PCT, HLA-DR), and cytokine levels (TNF-α, IL-6) were assessed before and after therapy. The primary endpoint was 28-day mortality.

Results. Baseline patient characteristics and laboratory parameters were comparable between the groups. The administration of ulinastatin significantly reduced 28-day mortality (10.0 % vs. 33.3 %; p< 0.01) and the number of new organ dysfunction cases (10 vs. 26; p = 0.003). Patients in the ulinastatin group showed an increase in ventilator-free days (18.4±7.4 vs. 12.2±5.1; p = 0.035) and a reduced mean hospital stay (by 13.6 days; p< 0.001). Patients in the ulinastatin group demonstrated a significant decrease in CRP, PCT, TNF-α and IL-6 levels, and an increase in HLA-DR levels (p< 0.05). Multivariate analysis confirmed ulinastatin use as an independent factor for reducing the risk of death (OR=0.45; 95 % CI: 0.21–0.74; p = 0.018).

Conclusions. The inclusion of ulinastatin in the comprehensive treatment of postoperative AS significantly suppresses the inflammatory response, improves clinical outcomes, and reduces 28-day mortality. These findings justify the use of ulinastatin in the management of this severe patient population and require confirmation in large randomized studies.

Objective. To determine the predictors of atrial fibrillation (AF) development in patients with ST-segment elevation myocardial infarction (STEMI).

Materials and methods. The study presents the results of the first (in-hospital) stage of a prospective, two-stage, open-label, observational clinical trial with a retrospective assessment of the patient data prior to their enrollment in the study. Over a 2-year period, 167 patients with STEMI were sequentially included into the study on admission to a multidisciplinary hospital according to the inclusion and exclusion criteria. To determine the predictors of AF development in STEMI patients, they were divided into 2 groups: Group 1 comprised 140 patients (83.8 %) with STEMI and no AF during hospitalization or in their medical history; Group 2 included 27 patients (16.2 %) with STEMI who experienced an AF paroxysm during hospitalization.

Results. The prevalence of AF among 167 hospitalized patients with STEMI was 16.2 % (n=27). In 9.6 % of cases, AF paroxysm was verified for the first time, while in 6.8 % it was a manifestation of a pre-existing paroxysmal form. Systolic blood pressure BP < 90 mmHg, heart rate < 50 bpm and >110 bpm, and Killip class >1 increased the relative risk (RR) of AF paroxysm in MI patients by 2.3-fold, 6.1-fold, and 3.0-fold, respectively. Comorbid conditions such as obesity, chronic heart failure, and a history of pulmonary pathology increased the RR of AF by 2.6-fold, 2.3-fold, and 2.2-fold, respectively. Pre-admission use of renin-angiotensin-aldosterone system (RAAS) blockers and beta-blockers reduced the RR of AF development by 71 %, whereas the need for insulin therapy increased by 3.1-fold. In addition to the well-known predictors of AF development in MI associated with cardiac and renal remodeling, new ones were identified: left atrial contractile dysfunction index < 40 %; left ventricular ejection fraction (LVEF)-to-indexed left atrial volume ratio < 1.1; cystatin-based glomerular filtration rate < 45 ml/min/1.73 m²; urinary albumin-to-creatinine ratio > 300 mg/g; and creatinine-to-LVEF ratio. These increased the RR by 7.1-fold, 6.7-fold, 2.7-fold, 3.1-fold, and 2.7-fold, respectively. Among the new biomarkers associated with AF development in MI, the following were identified: blood apolipoprotein B100 (ApoB100) concentration > 100 mg/dL; monocytes-to-high-density lipoprotein cholesterol ratio > 26.5; tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1) > 124.2 ng/ml; platelet-to-lymphocyte ratio > 212.1; inflammatory burden index >36.85; the combination of the GG genotype of the ApoB gene polymorphism Arg3500Gln (rs5742904) with the ID genotype of the fibrinogen alpha (FGA) gene polymorphism rs35496957. These increased the RR by 3.5-fold, 2.8-fold, 5.6-fold, 2.5-fold, 3.3-fold, and 3.6-fold, respectively.

Conclusions. The study confirmed the clinical and historical predictors of AF paroxysm development in patients with STEMI and identified novel predictors associated with coupled structural and functional remodeling of the left and right ventricles, in combination with renal dysfunction, lipid metabolism disorders involving the apolipoprotein system, tissue fibrosis due to increased TIMP-1 levels, activation of nonspecific inflammation, anemia and pathological polymorphism of the ApoB100 and FGA genes.

Objective. To investigate the clinical and historical characteristics, instrumental and laboratory findings in patients with infertility associated with ovarian endometriomas after surgical treatment, and to identify factors influencing fertility restoration.

Materials and methods. A total of 80 patients with a confirmed diagnosis of infertility associated with ovarian endometriomas were examined. The assessment included history taking, general and gynecological examinations, and ultrasound using a Logiq S8 device (USA) with an E8C-RS transvaginal probe (4–11 MHz) evaluating the pattern of ovarian involvement (unilateral or bilateral) and cyst sizes (cm). Clinical and laboratory testing comprised measurement of plasma concentrations of AXIN-1, CYFRA-21-1, and haptoglobin by enzyme-linked immunosorbent assay (ELISA) using SEC191Hu ELISA Kit (CLOUD-CLONE CORP, USA), ELISA Kit for Cytokeratin Fragment Antigen 21-1 (CLOUD-CLONE CORP, USA), and Human Haptoglobin ELISA Kit (Assaypro LLC, USA). Blood samples were collected before surgery, on postoperative day 10, and 6 months after surgical intervention. Surgical treatment was performed by laparoscopic approach using Karl Storz equipment (Germany) with salpingo-ovariolysis, cystectomy, chromotubation, and hysteroscopy. After a 12-month postoperative follow-up, patients were divided into two groups according to fertility restoration: those who achieved pregnancy (n = 35) and those who did not (n = 45). MedCalc software, version 23.2.1 (MedCalc Software Ltd., Belgium) was used for analysis and processing of quantitative data.

Results. Ultrasound examination revealed that bilateral ovarian involvement was associated with impaired restoration of natural fertility. Laboratory investigation demonstrated a negative correlation between AXIN-1 protein levels at six months post-surgery and the probability of pregnancy, as well as a positive correlation between CYFRA-21-1 levels at six months post-surgery and preoperative haptoglobin levels with pregnancy achievement. ROC analysis determined threshold values of the biomarkers for predicting fertility restoration: AXIN-1 ≤ 1.16 ng/mL, CYFRA-21-1 > 0.25 ng/mL, haptoglobin > 779 mg/L. Based on the identified statistically significant laboratory parameters (AXIN-1 and haptoglobin levels) and the pattern of ovarian involvement, along with additional predictors of lower statistical significance — **clinical history data** (chronic pelvic pain) and **ultrasound parameters** (total cyst size) — a prognostic model for fertility restoration was developed with a specificity of 79,1 % and an accuracy of 76,0 %.

Conclusions. A comprehensive assessment of clinical history, ultrasound, and laboratory data allowed the identification of key prognostic criteria for the restoration of reproductive function in patients with infertility associated with ovarian endometriomas. The developed prognostic model may serve as a valuable tool for determining the optimal treatment strategy for infertility in this patient cohort. However, further studies are needed to validate the model in larger samples and to assess its applicability in various clinical settings.

Objective. To retrospectively evaluate the effectiveness of magnetic resonance cholangiography (MRC) in diagnosing «minor» (type A) and «major» (types B-E) iatrogenic injuries of the extrahepatic bile ducts (EHBD) following cholecystectomy.

Materials and methods. Over a 10-year period, at the Perm Regional Clinical Hospital, MRC was performed in 52 patients who developed complications in the early postoperative period after cholecystectomy for calculous cholecystitis. The type of EHBD injury was classified according to the Bismuth-Strasberg classification. When «minor» type A injuries were detected, patients underwent endoscopic treatment, including endoscopic retrograde cholangiopancreatography (ERCP), papillotomy and EHBD stenting; relaparoscopy was performed, if necessary, For the diagnosis of "major" injuries, open surgery with Roux-en-Y hepaticojejunostomy was performed. The. MRC results were compared with the ERCP or surgical findings.

Results. MRC was performed in all patients 1-27 days after surgery. It enabled the diagnosis of cystic duct stump leakage (CDSL) in 27 cases and complete transection of the common bile duct (CBD) (20) or its clipping (5) at various levels in 25 cases. The main sign of CDSL on MRI cholangiograms was the presence of fluid near the cystic duct stump. In eleven patients with CDSL, biliary hypertension was detected due to stenosis of the major duodenal papilla, with (5) or without (6) choledocholithiasis. The accuracy of MRC in diagnosing CDSL was 96.29 %. In 20 patients, a complete transection of the EHBD at various levels was detected, in some cases (6), there was a significant bile duct tissue defect between its proximal and distal sections. Clipping of the EHBD was suspected in five cases based on the dilation of the bile duct and a blind termination of its distal part without fluid accumulation in the abdominal cavity. The level of intersection or clipping corresponded to E1 in 3 cases (12 %), E2 in 9 cases (36 %), E3 in 8 cases (32 %), E4 in 3 cases (12 %), and E5 in 2 cases (8 %). The accuracy of MRC in diagnosing "major" EHBD injuries was 100 %.

Conclusions. MRC performed in the early postoperative period enables the diagnosis of all types of EHBD injuries with an accuracy of 96–100 %.

Objective. To perform molecular genetic monitoring of HIV-1 drug resistance to integrase inhibitor (INIs) and to assess the prevalence of mutations associated with viral resistance to these drugs in the Volga Federal District (VFD) from 2021-2024.

Materials and methods. The study analyzed 121 blood plasma samples from HIV-infected patients experiencing virological failure of antiretroviral therapy (ART) with integrase inhibitors. The samples were delivered for HIV-1 drug resistance testing from ten subjects of the Volga Federal District: the Republics of Bashkortostan, Mari El, Mordovia, Udmurtia and Chuvashia, and Kirov, Nizhny Novgorod, Penza, Saratov and Ulyanovsk oblasts. HIV-1 genotyping was performed by fragment sequencing of reverse transcriptase, protease, and integrase regions of the HIV-1 pol gene. Information about the samples was obtained from test requisition forms for HIV-1 drug resistance testing provided by the regional AIDS prevention and control centers of the Volga Federal District.

Results. The number of HIV-infected patients receiving INIs-based antiretroviral therapies in VFD is increasing, reaching 22.1 % of all treated patients in 2023. The analysis of HIV-1 resistance to INIs revealed mutation combinations associated with resistance to second–generation INIs: R263RK, E138K+T66A+G118R, E138K+G140A+Q148R, E138K+G140A+S147G, S147G+N155H. The following risk factors for developing INIs resistance were determined: the HIV infection duration more than 15 years from the first positive Western blot result (p = 0.057), the age of HIV-infected patients over 35 years (p = 0.079), and existence of HIV-1 resistance to nucleoside reverse transcriptase (NRTIs), non-nucleoside reverse transcriptase (NNRTIs), or protease inhibitors (PIs) (p< 0.0001).

Conclusions. The growing proportion of HIV-infected patients receiving INIs-based antiretroviral therapies, including second–generation INIs, in the VFD underscores the necessity for regular molecular and genetic monitoring of HIV-1 resistance to INIs which is essential for further study of the prevalence of resistant viral strains to increase the effectiveness of ART.

Relevance. Rib pseudoarthrosis is a rare outcome of rib fractures, characterized by the absence of bony union and the formation of a pathological fibrous–osseous connection with mobility at the defect site. In some cases, herniation of lung tissue may occur. Although this complication is uncommon and reported only in isolated case reports and small series, it can result in significant pain, respiratory impairment, and ischemic changes in the pulmonary parenchyma. Determining the optimal management strategy for patients with this pathology remains a relevant and clinically significant issue in modern thoracic surgery.

Materials and methods. We present a clinical case of a 50-year-old patient hospitalized in a thoracic surgery center six months after an occupational injury, with rib pseudoarthrosis complicated by a lung hernia. On admission, the patient complained of persistent dull pain in the left chest and a palpable protrusion at the site of the pseudoarthrosis. For further diagnostic clarification, computed tomography with 3D reconstruction was performed. Video-assisted thoracoscopy was carried out to repair the lung hernia, combined with sequential stable fixation of the rib pseudoarthrosis. The operative time was 105 minutes, and blood loss was 50 mL. Preoperative imaging findings, the surgical procedure, and the postoperative outcomes are presented. At three months postoperatively, the patient reported no complaints; follow-up CT confirmed consolidation of the rib fractures and the absence of intrapleural complications. The total sick leave after surgery was 90 days, and the patient returned to his occupation as a truck driver.

Conclusions. This case report demonstrates the effectiveness of a surgical approach combining stable fixation of rib nonunion with simultaneous repair of an intercostal lung hernia. The observed outcomes support the appropriateness of surgical management for symptomatic rib pseudoarthrosis, particularly in cases complicated by lung herniation. This approach ensures reliable stabilization of the thoracic cage, alleviates pain, and reduces the risk of recurrent complications.

The article presents the historical stages of development of the Department of Epidemiology at Perm State Medical University named after Academician Ye. A. Vagner over 85 years. It outlines the evolution of technologies, forms, and methods used in the educational process. The paper also highlights the department’s scientific research areas and its experience in collaborating with healthcare authorities, medical institutions, and Rospotrebnadzor (the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing).